Positive selection drives lactoferrin evolution in mammals.

Lactoferrin (LF) is a member of the transferrin family that is abundantly expressed and secreted by glandular epithelial cells. The biological functions of LF involve in iron homeostasis regulation of the body and antibacterial activity. Previous studies demonstrated that it had a high cationic N-terminal domain that could interact with glycosaminoglycans, lipopolysaccharides and the bacterial virulence protein. Two anti-microbial peptides, lactoferricin (LFcin) and lactoferrampin (LFampin), were also isolated and identified in N-terminal of LF. Although the antibacterial mechanism was carefully studied, little was known about the molecular evolution of LF. In this study, we estimated the nonsynonymous-to-synonymous substitution ratios ( ) per site using maximum likelihood method to analyze the LF evolution. The results of omega > 1 and five identified positive selection sites of amino acid suggested that the evolution of LF gene was characterized by positive selection. Further study found that the positive selection sites were either located in the LF-bacteria binding region or the peptides of LFcin and LFampin, indicating that the selection pressure was related to LF-bacteria interaction. The identification of these sites may contribute to the mechanism of bacteria-LF interaction.